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Reference: Ananthaswamy N, et al. (2010) The signaling interface of the yeast multidrug transporter pdr5 adopts a cis conformation, and there are functional overlap and equivalence of the deviant and canonical q-loop residues. Biochemistry 49(21):4440-9

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Abstract


ABSTRACT: ABC transporters are polytopic proteins. ATP hydrolysis and substrate transport take place in separate domains and these activities must be coordinated through a signal interface. We previously characterized a mutation (S558Y) in the yeast multidrug transporter Pdr5 that uncouples ATP-hydrolysis and drug transport. We used a genetic screen to isolate second-site mutations of S558Y that restore drug-transport and thereby characterize the transmission interface. We recovered suppressors that restore drug resistance whose locations provide functional evidence for an interface in the cis rather than the trans configuration found from structural and crosslinking studies of bacterial and eukaryotic efflux transporters. One of the mutations: E244G defines the Q-loop of the deviant portion of NBD1 that is the hallmark of this group of fungal transporters. When moved to an otherwise wild-type background, this mutation and its counterpart in the canonical ATP-binding site Q951G show a similar reduction in drug resistance and in the very high basal-level ATP hydrolysis characteristic of Pdr5. A double E244G, Q951G mutant is considerably more drug sensitive than either of the singles. Surprisingly, then, the deviant and canonical Q-loop residues are functionally overlapping and equivalent in a strikingly asymmetric ABC transporter.

Reference Type
Journal Article
Authors
Ananthaswamy N, Rutledge R, Sauna ZE, Ambudkar SV, Dine E, Nelson E, Xia D, Golin JE
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